title: Effectiveness of Haemophilus influenzae type b vaccines administered according to various schedules: systematic review and meta-analysis of observational data.
abstract: BACKGROUND
  Conjugate vaccines against Haemophilus influenzae type b (Hib) are widely used. The full implications of Hib vaccination schedule for vaccine effectiveness (VE) are unclear.
  
  
  METHODS
  We searched the literature for observational studies reporting the effectiveness of conjugate Hib vaccines administered according to different schedules. We summarized dose-specific VE estimates, where appropriate, using random effects meta-analysis.
  
  
  RESULTS
  Thirty-one eligible articles (reporting 30 studies conducted in 17 countries) were identified. Meta-analysis of case-control studies using community controls produced VE estimates against Hib meningitis of 55% (95% confidence interval: 2-80%, based on 3 studies), 96% (86-99%, 3 studies) and 96% (86-99%, 4 studies) after 1, 2 and 3 doses of vaccines other than the polyribosyl ribitol phosphate outer membrane protein vaccine. Estimates were similar using hospital controls. VE against invasive Hib disease in case-control studies was estimated as 59% (30-76%, 3 studies) and 97% (87-99%, 3 studies) for 1 and 3 doses (insufficient data were identified to estimate 2-dose VE). Point estimates from 2 studies suggested VE>90% after 1 dose of the polyribosyl ribitol phosphate outer membrane protein vaccine, but meta-analysis was not possible. Using data from 4 cohort studies, 3-dose VE was estimated as 94% (88-97%). There was some evidence that Hib vaccine was less effective when administered with acellular (rather than whole cell) pertussis vaccine. Weak evidence from 2 studies suggested that a booster confers some additional protection following full primary vaccination and may compensate for an incomplete primary series.
  
  
  CONCLUSIONS
  Observational data suggest that ≥2 doses of Hib vaccine are required for high effectiveness, but do not strongly favor any particular schedule.
authors.affiliation: From the *Research Department of Infection and Population Health, University College London; †Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, United Kingdom.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Jackson
authors.forename: Andrea
authors.initials: A
authors.lastname: Mann
authors.forename: Punam
authors.initials: P
authors.lastname: Mangtani
authors.forename: Paul
authors.initials: P
authors.lastname: Fine
mesh_terms: D016022:Case-Control Studies; D006192:Haemophilus Infections / Q000453:epidemiology / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D019741:Haemophilus influenzae type b / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic
chemical_list: D018073:Haemophilus Vaccines